Alcohol use has been shown to have a profound effect on the immune system. Information regarding the impact of alcohol use on HIV immunocompromised individuals, however, is limited and controversial. With the advent of highly active combination therapy (HAART), alcohol related research in HIV infected subjects has mainly focused on the behavioral problems caused by alcohol intake including poor adherence to therapeutic regimens. In HIV infected patients, adherence levels below 95% have been associated with viral load rebound, limited immune response and drug resistance. Strict adherence to medication, is therefore critical if HIV infected patients are to benefit maximally from HAART. Of particular interest is a parallel phenomenon, showing that despite good adherence, some individuals do not demonstrate a robust immune and/or virological response. Several factors have been identified and include age of the patient and level of CD4 depletion at the time of HAART initiation. Our preliminary data indicate that "heavy alcohol use" may also influence the effectiveness of HAART treatment and ability to achieve a significant CD4 increase. The proposed Minority New Investigator application will evaluate the impact of "heavy alcohol use" (214-drinks/per week for men, >7drinks/per week in women) on immune function (thymus repletion) and response to antiretroviral treatment (CD4, viral load and mental status) in HIV/AIDS. In this longitudinal study, 115 HIV+ "heavy alcohol users" and 115 HIV+ "non-alcohol users" will be enrolled and followed over a 6-month period. Using standard questionnaires, a detailed sociodemographic, medical, alcohol use and HIV medication and adherence history will be obtained. The impact of alcohol on the effectiveness of HAART will be investigating by comparing thymus size, proportion and production naive cells CD4+ CD45RA+CD62L+ (thymic production), CD8, viral load and mental status at baseline and over time. We hypothesize that alcohol induced effects on the thymus may influence not only antiretroviral-based immune repletion, but also HIV-related cognitive alterations and may, therefore, affect the therapeutic benefits of HAART. Our long-term objectives are to extend biomedical knowledge related to alcohol use during HIV disease and provide biomedical information to develop therapeutic strategies for HIV infected subjects, particularly those who are also alcohol abusers.